Downregulation of the calcium current in human right atrial myocytes from patients in sinus rhythm but with a high risk of atrial fibrillation

Aims A decrease in L-type calcium current (I-CaL) is an important mechanism favouring atrial fibrillation (AF). Here, we aimed to identify pathogenic factors associated with I-CaL downregulation. Methods and results Atrial myocytes were isolated from right atrial appendages obtained from 86 adult patients in sinus rhythm with coronary artery disease, aortic valve disease, or mitral valve disease (MVD). Current was recorded in isolated myocytes using the whole-cell patch-clamp technique. The I-CaL recorded in the 172 myocytes studied showed a marked variability of peak density ranging from 0.1 to 9.0 pA/pF. The I-CaL peak density did not correlate with membrane capacitance or changes in current biophysical properties. The I-CaL peak density was homogeneous for a given sample. Small I-CaL values were recorded in patients with MVD or with a low left ventricular ejection fraction (< 45%). Small I-CaL values were more sensitive to the beta-adrenergic agonist, isoproterenol (1 mu M), and to the phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine (10 mu M). Conclusion In human atrial myocytes, the variability of I-CaL is related to the clinical history of the donors. The downregulation of I-CaL is already observed in patients in sinus rhythm with a high risk of AF and is associated with the greatest response to beta-adrenergic agonist.